This invention relates to an improved method of sealing a medical container, such as a vial containing a medicament, drug or vaccine, which eliminates the problems associated with malleable metal caps or collars, such as aluminum. The method of this invention may be used to seal a vial having an elastomeric stopper with a polymeric closure or collar. The method of this invention may also be used for sealing a vial or other medical container with a fluid transfer set separate from or integral with the collar portion of the closure.
It is conventional to store medicaments, drugs or vaccines in a sealed vial or other container for later use. Such medicaments, drugs or vaccines may be in a dry or powdered form to increase the shelf life of the drugs and reduce inventory space. Such dry or powdered medicaments, drugs or vaccines are generally stored in a sealed vial and reconstituted in liquid form for administration to a patient by adding a diluent or solvent. Alternatively, the medicament, drug or vaccine may be in liquid or even gaseous form. A conventional vial for storing medicaments generally includes an open end, a radial rim portion surrounding the open end and a reduced diameter neck portion adjacent the rim portion. The vial is conventionally sealed with an elastomeric stopper or septum which generally includes a tubular portion inserted into the neck of the vial and a planar radial rim portion which overlies the vial rim. The stopper is normally secured to the vial with a thin malleable metal cap, such as aluminum. The aluminum cap includes a tubular portion which surrounds the rim portions of the stopper and vial, an inwardly projecting annular portion which overlies the rim portion of the stopper and a distal end portion which is crimped radially into the vial neck beneath the vial rim portion. Because aluminum is malleable, the collar accommodates the buildup of tolerances of the dimensions of the stopper and vial rim. The dimensions and tolerances of standard vials and stoppers are set by the International Standards Organization (ISO).
The radial portion of the aluminum cap which overlies the stopper rim portion may be closed, in which case the aluminum cap is removed by xe2x80x9cpeelingxe2x80x9d the aluminum cap from the vial. A pre-slit tab located in the middle area may be provided which overlies the vial rim, permitting the cap to be torn from the top and peeled from the vial prior to use. This closed embodiment of an aluminum cap has several disadvantages. First, the tearing of the metal cap creates sharp edges which may cut or damage sterile gloves and cut the person administering the drug, thereby exposing both the healthcare worker and the patient to disease and contamination of the drug. Second, the tearing of the aluminum cap generates metal particles which may also contaminate the drug, medicament or vaccine. The dangers associated with the tearing of an aluminum cap has been solved in part by adding a xe2x80x9cflip-offxe2x80x9d plastic cap. In one such embodiment, the aluminum collar includes a central opening and a shallow plastic cup-shaped cap is received over the aluminum collar having a central projecting riveting portion which is received and secured in the central opening of the aluminum collar. The plastic cap is then removed by forcing the flip-off cap away from the aluminum collar, which tears an annular serrated portion surrounding the central opening and exposes an opening in the collar for receipt of a hypodermic needle or the like. This embodiment reduces but does not eliminate the possibility of tearing the sterile gloves of the healthcare worker. More importantly, however, aluminum dust is still created which may contaminate the medicament. It is also important to note that metallic dust is also created simply by forming and affixing the aluminum collar to the vial because aluminum dust is created in forming the aluminum collar, crimping of the collar and removal of the flip-off plastic cap.
Aluminum collars have also been used to secure a fluid transfer set on medicament vials. Transfer sets may be utilized, for example, to transfer fluid from a syringe to a vial, such as to reconstitute a dry or powdered drug in a vial by adding a diluent or solvent. The reconstituted drug may then be withdrawn from the vial by the syringe. The inner surface of the transfer set may be part of the drug fluid path and the aluminum collar or ring may bring aluminum particles in the sterile room where the drug is added to the vial or into the drug fluid path contaminating the drug. There have been attempts to reduce this problem by applying a coating, such as a polymeric coating, to the aluminum cap or collar. Finally, the prior art also includes snap-on cup-shaped plastic caps or collars having a radially inwardly projecting end portion which is snapped over the rim portion of the vial. Snap-on plastic collars, however, do not assure adequate sealing of the vial or fully accommodate the tolerances of standard vials and stoppers as required.
The need therefore remains for a method of sealing vials and other medical containers which may be utilized for sealing conventional medical containers, such as medicament vials or cartridges, which assures sealing of the container and which achieves a good level of cleanliness, without metal particles or dust which will contaminate the medicament, drug or vaccine, the transfer set or clean room and which does not expose the health care worker to sharp edges. The method of sealing a medical container of this invention eliminates these problems and permits sealing of medical containers in an aseptic environment.
As set forth above, the method of sealing a vial or other medical container with a plastic closure of this invention eliminates the problems associated with malleable metal or aluminum caps or collars, but which accommodates build-up of tolerances of the rim portion of the container and the elastomeric stopper, when used. The plastic or polymeric closure of this invention is relatively inexpensive to manufacture and use in the method of this invention. The method of this invention may be utilized to seal a conventional medical vial with a polymeric cap, a collar in combination with a flip-off cap or with a collar used to secure and seal a transfer set on a vial for transferring fluid between the vial and a second container, such as a hypodermic syringe. As used herein, the term xe2x80x9cclosurexe2x80x9d is generic to either a cap or collar alone or in combination with a transfer set.
As stated above, the method of sealing a container with a plastic closure of this invention may be utilized with a conventional vial or other medical container having an open end, a radial rim portion surrounding the open end and a reduced diameter neck portion adjacent the rim portion. The method of sealing a medical container with a plastic closure of this invention includes forming a plastic closure from a polymer, preferably formed by injection molding, which is sufficiently malleable to permit radial deformation, yet sufficiently rigid to retain its shape following deformation and sufficiently resistant to creep to maintain a seal between the plastic closure and the container following radial deformation. The plastic closure formed by the method of this invention includes a generally cylindrical tubular portion having an internal diameter generally equal to or preferably slightly greater than an outside diameter of the rim portion of the container and an integral radial rim portion. In the preferred method of this invention, the plastic closure is formed by injection molding a polymer alloy comprising a relatively malleable soft polymer and a relatively rigid polymer. The closure may be formed by co-injecting a polymer alloy which preferably includes a polycarbonate as the relatively rigid polymer.
The method of this invention then includes telescopically disposing the tubular portion of the closure over the rim portion of the container with the radial rim portion of the closure overlying the rim portion of the container and the generally cylindrical tubular portion surrounding the container rim having a free end surrounding the reduced diameter neck portion of the container. The tubular portion of the closure adjacent the free end is then deformed radially inwardly into the neck portion of the container beneath the rim portion and preferably against the rim portion adjacent the neck portion, permanently securing the closure on the container and sealing the container open end, wherein the free end of the plastic closure retains its shape beneath the radial rim portion following deformation and the polymer is sufficiently resistant to creep to permanently maintain the seal. In the preferred method of sealing a vial having medicament, drug or vaccine therein, the vial is initially sealed with an elastomeric stopper having a tubular portion received in the open end of the vial and a planar rim portion which overlies the rim portion of the vial. The method of this invention then preferably includes compressing the radial rim portion of the plastic closure against the radial portion of the stopper to seal the plastic closure to the stopper and substantially simultaneously radially deforming the free end of the closure tubular portion into the reduced diameter neck portion of the vial as described above.
In the preferred method of sealing a container, such as a medical vial, with a plastic or polymeric closure of this invention, the cylindrical tubular portion of the closure is deformed radially into the neck portion of the container using a crimping tool having an inclined, chamfered or tapered surface and the vial or container and the crimping tool are relatively rotated and driven together to deform the tubular portion of the closure both radially into the neck portion of the collar and axially against the adjacent rim portion of the container to permanently secure the closure on the container and seal the container. In one preferred embodiment of the method of this invention, the crimping tool includes a frustoconical chamfered surface which is rotated and driven against the tubular portion of the closure, crimping the collar as described. In this embodiment, the container or vial may be simultaneously rotated to crimp and seal the entire periphery of the rim portion. In another embodiment, the crimping tool includes an arcuate or circular stationary rail having an inclined or frustoconical chamfered surface and the method of crimping the closure includes simultaneously driving the vial and closure assembly against the rail and rotating the vial to crimp the tubular portion of the closure radially inwardly into the reduced diameter neck portion and axially against the adjacent rim portion of the container as described. In either embodiment, the method is preferably a cold forming process dependent upon the material of the polymeric closure, which as described as above is sufficiently malleable to permit radial deformation, yet sufficiently rigid to retain its shape following deformation and sufficiently resistant to creep to maintain the seal between the plastic closure and the container following radial deformation.
In both preferred embodiments of cold forming the free end of the plastic closure into the reduced diameter neck portion of the vial or other container, the free end of the tubular collar portion is preferably gradually or incrementally deformed radially into the neck portion to assure permanent deformation, reduced creep and reduce damage to the closure, such as stress cracking or discoloration of a clear plastic closure. In the first embodiment of the method of this invention described above, the free end of the tubular closure is deformed incrementally by a series of rotating crimping tools, wherein the first tool has a relatively steep angle of inclination, such as 45 degrees. The angle of inclination of the next crimping tool is then reduced, etc. to the desired angle of the deformed lip, which may be, for example, 20 to 30 degrees. In the second embodiment of the method of this invention described above, the angle of inclination of the crimping surface of the rail is gradually reduced as the vial or other container is rolled or rotated along the rail gradually cold forming the free end of the closure and avoiding damage to the closure including cracking and discoloration.
Where the method of sealing a vial or other medical container of this invention is utilized to seal a transfer set on a vial or other medical container, the closure may take the form of a collar having a second tubular portion extending from the radial rim portion of the collar, generally coaxially aligned with the tubular collar portion received on the rim portion of the container. In the method of sealing a transfer set on a vial or other medical container, the components of the transfer set are assembled before crimping of the collar on the medical container, preferably in an aseptic or sterile environment. In the preferred embodiment, the transfer set includes a piercing member which is telescopically supported in the second tubular portion of the closure for piercing an elastomeric stopper in the open end of the container or vial. One important advantage of the method of sealing a vial or other medical container of this invention is that the container may be a conventional medical vial, as described above, having a conventional elastomeric stopper. A conventional elastomeric stopper has a tubular portion which is press fit into the open end of the vial and a radial planar portion which overlies the rim portion of the vial. The transfer set may also include a tubular transfer member which telescopically receives the piercing member and which may be integral with the second tubular portion of the closure or separate from the collar portion and secured by the collar portion. Finally, the preferred embodiment of the transfer set also includes a cap which seals the open end of the second tubular portion of the collar.
The method of sealing a transfer set on a vial or other medical container with a plastic closure of this invention then includes first assembling the transfer set, including telescopically supporting the piercing member within the second tubular portion of the closure. As described above, the closure includes a tubular collar portion having an inside diameter generally equal to or preferably slightly greater than the outside diameter of the radial rim portion of the container or vial, a radial portion and a second tubular portion which is coaxially aligned with the tubular collar portion of the closure. The closure is then assembled on the vial or other medical container by telescopically receiving the tubular collar portion of the closure over the rim portion of the container such that the tubular collar portion surrounds the rim portion of the container and at least a portion of the reduced diameter neck portion. The second tubular portion of the closure and the piercing member are now coaxially aligned with the open end of the vial or other medical container and moveable relative to the elastomeric stopper to pierce the stopper. The method of this invention then includes radially deforming the tubular collar portion of the closure adjacent the free end into the reduced diameter neck portion of the container and against the adjacent radial rim portion, permanently securing the closure on the container and sealing the container as described above. That is, the tubular collar portion is preferably gradually or incrementally deformed or cold formed as described above. In the most preferred embodiment of the method of sealing a transfer set on a vial of this invention, the radial portion of the closure is simultaneously compressed against the radial planar rim portion of the elastomeric stopper as the tubular collar portion is crimped in the neck portion of the container and the piercing member is telescopically supported in the second tubular portion of the closure for telescopic movement to pierce the planar rim portion of the elastomeric stopper and provide fluid communication between the vial or other medical container and the tubular transfer portion of the transfer set. The tubular transfer member may also include a Leur threaded connection for receipt of a threaded Leur connection of a second container, such as a syringe.
As set forth above, the method of sealing a container with a plastic closure of this invention utilizes a polymer for the closure having the requisite physical properties to provide and maintain a seal between the plastic closure and the vial or other medical container and permanently secure the closure on the container. In the preferred embodiment, the plastic closure is formed of a polymer alloy or melt blend which includes a relatively tough soft malleable copolymer and a relatively rigid copolymer. In the most preferred embodiment, the composite polymer is a polymeric alloy of a relatively soft malleable copolymer and a relatively rigid polymer. The preferred rigid polymer is a polyamid or a polycarbonate and the preferred relatively soft copolymer may be selected from polyesters or polyolefins. The resultant polymer alloy or composite preferably has an elongation at yield between 5% and 10% and an elongation at break greater than 100% with a flectural modulus of greater than 1,900 MPa.
The method of this invention thus eliminates the problems and hazards associated with the use of a malleable metal closure or collar, such as aluminum, and plastic coated aluminum caps or collars while assuring sealing of the container or damage to the plastic closure. In the most preferred embodiment of the method of this invention, the plastic closure or collar is formed by injection molding the plastic closure from a polymeric alloy or composite as described. A thermoplastic elastomer may also be co-injected with the polymer forming the closure to form a coating or film on the inside surface of the closure, which is integrally bonded to the polymer of the closure. As used herein, the terms xe2x80x9ccompositexe2x80x9d and xe2x80x9calloyxe2x80x9d are used in their broadest sense to include alloys or melt blends, composites and copolymers.
Other advantages and meritorious features of the method of sealing a vial or other medical container with a plastic closure or collar of this invention will be more fully understood from the following description of the preferred embodiments, the appended claims and the drawings, a brief description of which follows.